The fusion of perigranular membranes with the plasma membrane, and the liberation of arachidonic acid from membrane lipids result in the release of mediators of immediate hypersensitivity from mast cells. We propose to extend our studies of these reactions in several ways. The nature and subcellular distribution of relevant enzymes will be examined. Phospholipase C, phospholipase D, phospholipase A2, phosphatidate phosphohydrolase, diglyceride kinase, diglyceride lipase, and monoglyceride lipase enzymes will be studied. The effects of cyclic nucleotide and calcium on these critical mast cell enzymes will be investigated. Alterations in phospholipid and neutral lipid metabolism in rat and hamster mast cells associated with stimulation by antigen-IgE interactions, anaphylatoxins or kinins will be analyzed. We have sufficient preliminary data to predict that these will be feasible, fruitful studies. Several reactions essential to the mediator release process are likely to be identified. These studies may contribute to the purposeful development of pharmacologic agents capable of suppressing allergic reactions.